THE IMMUNE-RESPONSE TO 52-KDA RO AND 60-KDA RO IS LINKED IN EXPERIMENTAL AUTOIMMUNITY

Clustering of autoantibody specificities is a consistent finding in pa tients with systemic autoimmune diseases, Patients with Sjogren's synd rome frequently have autoantibodies to La, 60-kDa Ro(SS-A) protein (Ro 60), and 52-kDa Ro(SS-A) protein (Ro52), In the case of anti-Ro60 and anti-La, there is evidence that these specificities occur together bec ause of the physical association of the Ro60 and La proteins that form a ribonucleoprotein particle (RNP), Thus the autoantibody response ma y spread from a single epitope to involve new epitopes located within other components of the RNP. The physical association of Ro52 with the Ro/La RNP has remained controversial, implying that Abs to Ro52 are n ot a consequence of intermolecular spreading and may be triggered inde pendently of the anti-Ro60 response. To examine this relationship of t he immune response to Ro52 and Ro60, mice were immunized with recombin ant Ro52, Ro60, or La, and examined for autoantibody production. Immun ization with Ro52 resulted in rapid, high titer Ab production to Ro52, followed 7 to 14 days later by lower titer autoantibody production to Ro60, Immunization with Ro60 led to anti-Ro60, which was also followe d 7 to 14 days later by a lower titer anti-Ro52 response, Cross-reacti vity of affinity-purified Abs from immune mouse sera was not observed. These observations suggest that the autoimmune responses to Ro60 and Ro52 are linked intrinsically, despite previous evidence suggesting th ey are not associated in vivo, The mechanism of linkage remains unclea r, but the data are most consistent with some physical association of Ro52 and Ro60 allowing autoimmunization, presumably as a result of nor mal cell turnover or specific injury in vivo.